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Evaluation of Sustained-release Dosage Form with Novel Metformin Salts

새로운 메트포르민 산부가염을 이용한 서방성 제형 평가

  • Kim, Dong-Wook (Department of pharmaceutical Engineering, Cheongju University)
  • Received : 2015.07.23
  • Accepted : 2015.11.06
  • Published : 2015.11.30

Abstract

In this study, metformin hydrochloride for first choice of type 2 diabetes patient is administered relatively high dose, 1000 to 2000 mg orally once a day, and had very high water solubility, so it make difficult to swallow tablet to requires high amount of sustained release agent. To overcome these challenges, we used novel metformin salts had relatively low water solubility to minimize sustaining excipient for small size of dosage form. six novel metformin salts were synthesized by making metformin free form under reaction with NaOH and adding acid salts. we confirmed metformin stearate had the lowest water solubility and showed half drug release in dissolution study at 12hour. In conclusion, novel metformin salts had low water solubility can be used to reduce the size of sustained metformin tablet for improving patient compliance.

본 논문에서는 제 2형 당뇨병의 1차 선택약으로 사용되는 메트포르민 염산염이 통상적으로 1일 1000mg~2000mg의 고용량으로 투여되고 동시에 매우 높은 수성용해도를 가지므로 1일 1회 복용을 위한 약물방출제어시스템에 다량의 서방성 부형제를 필요로 하여 제형의 크기가 커져 복용이 어려운 문제점이 있다. 따라서 이를 개선하고자 상대적으로 수성용해도가 낮은 새로운 메트포르민 산부가염을 합성하여 서방성 정제에 적용하여 메트포르민의 방출을 확인하고자 하였다. 이를 위해 메트포르민 염산염을 원료로 하여 NaOH하에서 메트포르민 base를 만들고 여기에 산부가염을 반응시켜 6개의 새로운 메트포르민 산부가염들을 합성하였다. 또한 이들의 수성용해도를 측정하여 메트포르민 염산염에 비해 현저히 낮은 수성용해도를 가지는 메트포르민 스테아린산염을 확인하였고 메트포르민 서방성 제형에 적용하여 실제 약물의 방출제어에도 용출시험 결과, 12시간에서 약 2배의 약물방출제어 효과를 확인하였다. 결론적으로 새로운 메트포르민 산부가염을 통해 서방성 부형제의 양을 줄여 제형의 크기를 줄임으로써 보다 높은 환자의 복약순응도를 기대할 수 있을 것이다.

Keywords

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